Nuclear factor gene transcriptions

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Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens.[1][2][3][4][5] NF-κB plays a key role in regulating the immune response to infection. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory.[6][7][8][9][10][11]

DNA binding sites

The "natural 11 bp 𝜿B binding site MHC H-2 [is 3'-CCCCTAAGGGG-5'] which is well ordered in our structure."[12]

Nuclear factor genes

Gene ID: 4790 is NFKB1 nuclear factor kappa B subunit 1 on 4q24: "This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappa-B (NFKB) protein complex. NFKB is a transcription regulator that is activated by various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and bacterial or viral products. Activated NFKB translocates into the nucleus and stimulates the expression of genes involved in a wide variety of biological functions. Inappropriate activation of NFKB has been associated with a number of inflammatory diseases while persistent inhibition of NFKB leads to inappropriate immune cell development or delayed cell growth. Alternative splicing results in multiple transcript variants encoding different isoforms, at least one of which is proteolytically processed."[13]

  1. NP_001158884.1 nuclear factor NF-kappa-B p105 subunit isoform 2 proprotein: "Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is 1 amino acid shorter than isoform 1. Variants 2 and 3 encode the same isoform (2)."[13]
  2. NP_001306155.1 nuclear factor NF-kappa-B p105 subunit isoform 2 proprotein: "Transcript Variant: This variant (3) differs in its 5' UTR and uses an alternate in-frame splice site in the 5' coding region compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is 1 amino acid shorter than isoform 1. Variants 2 and 3 encode the same isoform (2)."[13]
  3. NP_003989.2 nuclear factor NF-kappa-B p105 subunit isoform 1: "Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1). This isoform (1) may undergo proteolytic processing similar to that of isoform 2."[13]

Gene ID: 5970 is RELA RELA proto-oncogene, NF-kB subunit, aka NFKB3 on 11q13.1: "NF-kappa-B is a ubiquitous transcription factor involved in several biological processes. It is held in the cytoplasm in an inactive state by specific inhibitors. Upon degradation of the inhibitor, NF-kappa-B moves to the nucleus and activates transcription of specific genes. NF-kappa-B is composed of NFKB1 or NFKB2 bound to either REL, RELA, or RELB. The most abundant form of NF-kappa-B is NFKB1 complexed with the product of this gene, RELA. Four transcript variants encoding different isoforms have been found for this gene."[14]

  1. NP_001138610.1 transcription factor p65 isoform 2: "Transcript Variant: This variant (2) uses an alternate in-frame acceptor splice site at one of the coding exons compared to transcript variant 1. This results in a shorter isoform (2) missing a 3 aa segment compared to isoform 1."[14]
  2. NP_001230913.1 transcription factor p65 isoform 3: "Transcript Variant: This variant (3) uses an alternate in-frame splice site at the 5' end of the last exon compared to variant 1. The resulting isoform (3) lacks an alternate internal segment compared to isoform 1."[14]
  3. NP_001230914.1 transcription factor p65 isoform 4: "Transcript Variant: This variant (4) lacks an alternate internal in-frame segment in the last exon compared to variant 1. The resulting isoform (4) lacks an alternate internal segment compared to isoform 1."[14]
  4. NP_068810.3 transcription factor p65 isoform 1: "Transcript Variant: This variant (1) represents the predominant transcript and encodes the longer isoform (1)."[14]

See also

References

  1. Gilmore TD (October 2006). "Introduction to NF-kappaB: players, pathways, perspectives". Oncogene. 25 (51): 6680–4. doi:10.1038/sj.onc.1209954. PMID 17072321.
  2. Brasier AR (2006). "The NF-kappaB regulatory network". Cardiovascular Toxicology. 6 (2): 111–30. doi:10.1385/CT:6:2:111. PMID 17303919.
  3. Perkins ND (January 2007). "Integrating cell-signalling pathways with NF-kappaB and IKK function". Nature Reviews Molecular Cell Biology. 8 (1): 49–62. doi:10.1038/nrm2083. PMID 17183360.
  4. Gilmore TD (November 1999). "The Rel/NF-kappaB signal transduction pathway: introduction". Oncogene. 18 (49): 6842–4. doi:10.1038/sj.onc.1203237. PMID 10602459.
  5. Tian B, Brasier AR (2003). "Identification of a nuclear factor kappa B-dependent gene network". Recent Progress in Hormone Research. 58: 95–130. doi:10.1210/rp.58.1.95. PMID 12795416.
  6. Albensi BC, Mattson MP (February 2000). "Evidence for the involvement of TNF and NF-kappaB in hippocampal synaptic plasticity". Synapse. 35 (2): 151–9. doi:10.1002/(SICI)1098-2396(200002)35:2<151::AID-SYN8>3.0.CO;2-P. PMID 10611641.
  7. Meffert MK, Chang JM, Wiltgen BJ, Fanselow MS, Baltimore D (October 2003). "NF-kappa B functions in synaptic signaling and behavior". Nature Neuroscience. 6 (10): 1072–8. doi:10.1038/nn1110. PMID 12947408.
  8. Levenson JM, Choi S, Lee SY, Cao YA, Ahn HJ, Worley KC, Pizzi M, Liou HC, Sweatt JD (April 2004). "A bioinformatics analysis of memory consolidation reveals involvement of the transcription factor c-rel". The Journal of Neuroscience. 24 (16): 3933–43. doi:10.1523/JNEUROSCI.5646-03.2004. PMID 15102909.
  9. Freudenthal R, Locatelli F, Hermitte G, Maldonado H, Lafourcade C, Delorenzi A, Romano A (February 1998). "Kappa-B like DNA-binding activity is enhanced after spaced training that induces long-term memory in the crab Chasmagnathus". Neuroscience Letters. 242 (3): 143–6. doi:10.1016/S0304-3940(98)00059-7. PMID 9530926.
  10. Merlo E, Freudenthal R, Romano A (2002). "The IkappaB kinase inhibitor sulfasalazine impairs long-term memory in the crab Chasmagnathus". Neuroscience. 112 (1): 161–72. doi:10.1016/S0306-4522(02)00049-0. PMID 12044481.
  11. Park HJ, Youn HS (March 2013). "Mercury induces the expression of cyclooxygenase-2 and inducible nitric oxide synthase". Toxicology and Industrial Health. 29 (2): 169–74. doi:10.1177/0748233711427048. PMID 22080037.
  12. Patrick Cramer, Christopher J. Larson, Gregory L. Verdine and Christoph W. Müller (1 December 1997). "Structure of the human NF‐κB p52 homodimer‐DNA complex at 2.1 Å resolution". The EMBO Journal. 16 (23): 7078–90. doi:10.1093/emboj/16.23.7078. Retrieved 3 May 2020.
  13. 13.0 13.1 13.2 13.3 RefSeq (February 2016). "NFKB1 nuclear factor kappa B subunit 1 [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 3 May 2020.
  14. 14.0 14.1 14.2 14.3 14.4 RefSeq (September 2011). "RELA RELA proto-oncogene, NF-kB subunit [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 3 May 2020.

External links

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